Mesylate groups, benzyl hydrogenolysis

Hydrolysis of the acetonide and oxidative cleavage of the resulting diol 748 produces acid 749. Amide formation, mesylation of the alcohol, and hydrogenolysis of the benzyl groups produces an intermediate hydroxamate that intramolecularly displaces the mesylate group with inversion of configuration to form the dihydroisoxazole ring of 751. 

Hydrogenolysis of the C-7 benzyl ether, followed sequentially by selective triethylsilylation of the newly liberated C-7 hydroxyl and mesylation of the C-5 secondary hydroxyl, provides compound 34 in 60% overall yield (see 33—>34, Scheme 6). On the basis of Potier s studies,35 it was hoped that the C 20 hydroxyl group,... 

On the other hand, removal of the silyl group in 22 with fluoride ion and subsequent mesylation afforded 25. Hydrogenation of 25 followed by cychzation in the presence of sodium acetate and subsequent protection of the amino group with Cbz, treatment with ethanethiol in aqueous TFA, followed by dibenzylation, mercuric chloride catalyzed hydrolysis, sodium borohydride reduction and mesylation afforded 26. Selective hydrogenolysis of the carbamate group in 26 followed by intramolecular cyclization afforded the 3,5-di-O-benzyl ether of quinuclidinediol. Removal of the benzyl groups afforded 2. 

Introduction of the second nitrogen substituent is accomplished by mesylation of the secondary alcohol and subsequent displacement (with inversion) by sodium azide. Hydrolysis of the carbamate, hydrogenolysis of the N-benzyl group with concomitant reduction of the azide group, protection of the newly formed amino group with a Cbz, and ruthenium-catalyzed cyclization gives the hemiacetal 493, which is then carried on to the target molecule 494. 

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